New Perspectives in Inflammatory Bowel Disease
Moderators: Dr. Stanley Hamilton and Dr. Carolyn C. Compton
Section 4 -
What Histological Analysis of Pouches and Diverted Bowel Can and Cannot Do
Neil A Shepherd
There are three principle issues to consider when assessing an inflammatory condition of the
intestines pathologically. These are context, context and context. This is especially so when the
intestines have been subjected to surgery. That surgery creates a new milieu in which adaptive and/or
inflammatory changes provide confounding and confusing histological appearances (Warren & Shepherd,
2000). For, d espite its relative heterogeneity, the intestinal mucosa has a limited repertoire of
response to changing environments and injurious agents: similar histological appearances can be produced
by any number of aetiopathogenetic agents, demanding exact clinical, radiological and endoscopic
correlation to attain the correct diagnosis. Both ileal pouches and diverted colorectum are associated
with inflammatory changes in the mucosa of the intestine that are prone to misinterpretation by
pathologists: this may have major implications for the management of individual patients. This treatise
will consider five of the important areas where histological assessment may provide information of
fundamental importance for the further management of the patient but may yet provide confusing and
1. Does pouch histology aid in the differentiation of the inflammatory diseases that affect it?
Restorative proctocolectomy with ileal reservoir, known as ileal pouch-anal anastomosis in North
America , has become a leading surgical procedure for patients with ulcerative colitis and familial
adenomatous polyposis (FAP) requiring total colectomy. Pouch creation has provided pathologists with a
whole new field of study. Not unsurprisingly, the pouch acts as a neorectum and morphological changes
familiar to pathologists in the rectum also affect the reservoir (Warren & Shepherd, 1993; Yantiss
& Odze, 2006). Once the reservoir is established, it shows a form of mucosal adaptation (Shepherd et
al 1987; de Silva et al 1991; Setti Carraro et al 1994; Veress et al, 1995). Varying degrees of chronic
inflammation and architectural abnormality (villous flattening or partial villous atrophy) are found in
almost all (>90%) established pelvic ileal reservoirs (Shepherd et al, 1987). When villous atrophy is
severe, there is crypt hyperplasia although there is a lack of the intraepithelial lymphocytic infiltrate
that characterises coeliac disease (Shepherd et al, 1987; de Silva et al, 1991). These changes are
almost universal: they are much more pronounced in ulcerative colitis patients than those with FAP
(Shepherd et al, 1987). It is very important not
to equate such common inflammatory changes with a diagnosis of pouchitis.
The adaptive changes have been designated colonic phenotypic change (Shepherd et al, 1993) since the
villous atrophy and crypt hyperplasia produces an appearance resembling colon. This may be due to
changed faecal flora, although some have suggested the changes are not necessarily adaptive but are,
instead, the direct result of inflammation (Fruin et al, 2003). The concept of colonic phenotypic change
is supported by studies of mucin and lectin histochemistry, immunohistochemistry, mucin biochemistry and
electron microscopy (Warren & Shepherd, 2000). Pouches retain some properties of small bowel mucosa,
for instance disaccharidase activity (de Silva et al 1991). Because of this, the term colonic phenotypic
change is preferred to colonic metaplasia.
Studies have classified these adaptive changes, in ulcerative colitis patients, into three groups and
it appears that the amount of inflammatory/adaptive change is remarkably consistent both within
individuals and with time (Setti Carraro et al 1994, 1998; Veress et al 1995). Firstly about 50% of UC
patients maintain a relatively healthy reservoir mucosa throughout the life of the pouch with minor
villous changes, modest chronic inflammation and minimal active inflammation. A second group comprising
about 40% of patients shows intermittent inflammatory changes with reasonable architectural recovery.
The third group comprising between 10-20% of the total UC patient group have a flat and chronically
inflamed mucosa between acute exacerbations of active inflammation (Setti Carraro et al 1994, 1998;
Veress et al 1995). Biopsies taken within the first 6 months of reservoir construction will determine
which of the three groups an individual patient falls into and this should therefore give a useful guide
to those patients who demand the most rigorous surveillance (Setti Carraro et al, 1994).
Patients who inadvertently undergo pouch surgery for Crohn's disease are at risk of developing the
changes of Crohn's disease in their reservoir (Lucarotti et al, 1995). Histologically these changes will
resemble Crohn's disease elsewhere in the gut. Nevertheless care is required because any of the
individual histological features of Crohn's disease may be seen in the reservoir in patients who do not
have Crohn's disease. For instance granulomas are a characteristic feature of reservoir mucosa, usually
seen in the centre of lymphoid follicles, both associated with and without pouchitis (Shepherd, 1990).
It must be emphasised, however, that the only detailed study of granulomas in the pouch has concluded
that they still remain highly predictive for a diagnosis of Crohn's disease (MacNeill et al, 2004).
Granulomas may also be seen in the mucosa as a result of ruptured crypts and deep within the wall in
relation to suture material (Warren & Shepherd, 1993). Vertical fissures resembling those of Crohn's
disease may also be seen in pouch mucosa in relation to ruptured deep crypt abscesses and at anastomosis
lines, a feature also seen in the defunctioned rectum in ulcerative colitis (Warren et al, 1993).
Fistulae may occur soon after reservoir construction, particularly at suture lines. Crohn's-like
complications of the pelvic ileal reservoir may also include anal strictures, perianal abscesses and
colovaginal fistulae: all of these may occur in patients with an unequivocal pre-operative diagnosis of
ulcerative colitis (Goldstein et al, 1997). This author firmly believes that the diagnosis of Crohn's
disease should never be made on the histological appearances seen in the reservoir alone. A change in
diagnosis at this stage has grave consequences for the patient and should always be substantiated by
examination of the original proctocolectomy specimen or by further examination and investigation of the
remaining alimentary tract (Warren & Shepherd, 1993; Goldstein et al, 1997). Context, as ever,
This treatise cannot hope to cover all pathological entities seen in the pelvic pouch. Important
amongst these are mucosal ischaemia, mucosal prolapse, secondary pouchitis, pre-pouch ileitis and
cuffitis. The interested reader is referred to other reviews for discussion of these (Warren &
Shepherd, 1993 & 2000)
2. Is pouch mucosal histology useful in determining the cause of pouchitis and in its prediction, diagnosis and management?
Pouchitis is the commonest and most important complication of restorative proctocolectomy (Mortensen
& Madden, 1993; Sandborn & Pardi, 2004). It remains the most enigmatic condition in terms of
pathogenesis, management and prognosis. Many of the uncertainties concerning this disease are because of
poor understanding of 'normality' and a lack of uniform criteria for the diagnosis of pouchitis (Warren
& Shepherd, 1993; Sandborn & Pardi, 2004). Indeed the term itself, despite its widespread usage,
is a poor one that is open to misinterpretation. In the past the term pouchitis has been too loosely
applied: many different inflammatory diseases cause active inflammation in the reservoir and have been
called pouchitis. The term should be restricted to those patients with an acute-on-chronic, relapsing
inflammatory and ulcerating condition of the functioning reservoir with characteristic clinical,
endoscopic and pathological features (Mortensen & Madden, 1993). Definition problems account for the
wide spectrum of prevalence rates of pouchitis from different centres and differing response rates to
treatment (Shepherd, 1995). Because of the confusion over terminology, some now consider 'chronic
relapsing pouchitis' to be a more appropriate appellation for this condition. Symptomatology includes
diarrhoea, often bloody, abdominal pain, urgency, discharge, bloating and systemic symptoms: thus the
clinical features are not dissimilar to those of the disease for which pouch surgery was performed,
ulcerative colitis. Endoscopic examination in pouchitis patients reveals increased vascularity, contact
bleeding and ulceration, typical features of active chronic inflammatory bowel disease.
Whilst several conditions cause active inflammation in the reservoir, the pathological hallmarks of
pouchitis are acute inflammation and focal ulceration, occurring on a background of marked chronic
inflammation and villous atrophy. As one would expect from a chronic ulcerating condition of the small
bowel, ulcer-associated cell lineage/pseudopyloric metaplasia is a characteristic marker of the disease
(Warren & Shepherd, 1993). The overall histological appearances of pouchitis bear a close likeness
to those of ulcerative colitis and are unlike those of Crohn's disease. There is no doubt that histology
can predict those patients who are likely to suffer pouchitis. As has been discussed above, it is those
patients with 'type C' inflammatory changes (vide supra; Setti Carraro, 1994 & 1998; Veress et al,
1995). The evidence is clear that it is these patients who are most likely to suffer chronic relapsing
pouchitis and it is these patients who should be closely surveyed and, perhaps, treated prophylactically
to reduce the prevalence of pouchitis.
Once the clinical, endoscopic and histopathological characteristics are present, the diagnosis of
pouchitis is effectively established. When so defined the prevalence usually varies between 10% and 20%
of patients, although striking variations in prevalence rates continue to characterise the ileal
reservoir literature. Whilst there are firmly established links between the adaptive pathological
changes in the reservoir and subsequent pouchitis, the literature espouses several different theories as
to the cause of pouchitis (Warren & Shepherd, 1993 & 2000). Suggested pathogenetic mechanisms
have included stasis, bacterial changes with or without mucolysis, mucosal ischaemia, mucosal prolapse,
Crohn's disease, mucosal pathology as a result of a lack of small intestinal nutrients and recurrent
ulcerative colitis in a reservoir with colonic phenotypic change. Whilst the theorem that stasis and
bacterial changes could cause pouchitis is supported by the relative success of metronidazole, other
antibiotics and probiotics in the treatment and prevention of pouchitis (Mimura et al, 2004; Sandborn
& Pardi, 2004), it would seem that these are important for the chronic mucosal changes/adaptation but
that additional factors are required to produce pouchitis (Warren & Shepherd, 1993).
There are notable associations between an original diagnosis of ulcerative colitis and pouchitis.
The most favoured hypothesis for the cause of pouchitis is that it represents a re-emergence of
ulcerative colitis in reservoirs with colonic metaplasia/colonic phenotypic change (Warren &
Shepherd, 1993; Luukonnen et al, 1994). Most accept that pouchitis is essentially a disease of
ulcerative colitis patients and not of FAP patients. There are intriguing associations between
ulcerative colitis, extra-intestinal manifestations and pouchitis (especially primary sclerosing
cholangitis and arthritis)(Lohmuller et al, 1990; Penna et al, 1996; Hata et al, 2003). Like ulcerative
colitis, pouchitis shows a strong negative association with smoking (Merrett et al, 1996). Although
there is no evidence of a link between the prevalence of pouchitis and pre-existing backwash ileitis
(Gustavsson et al, 1989) or the extent of colitis in the proctocolectomy specimen (Samarasekara et al,
1996), re-emergence of ulcerative colitis in ileal mucosa, which has undergone phenotypic change, remains
the most favoured theorem for the pathogenesis of pouchitis (Warren & Shepherd, 1993 & 2000).
The most contentious facet of this theorem is the significance and the importance of colonic phenotypic
change in the mucosa. As already indicated, current evidence would suggest that 'colonic metaplasia' is
not complete in the reservoir: it is this area of reservoir mucosal pathophysiology that demands further
3. Can pouch histology predict those at high risk from pouch and cuff neoplasia?
The concept of proctocolectomy is to remove all potentially neoplastic tissue in both ulcerative
colitis and FAP patients. Nevertheless the surgery neither removes all colorectal mucosa nor abrogates
the neoplastic potential, particularly in FAP, in which adenomas are increasingly seen in the ileal
mucosa of the reservoir (Nugent et al, 1993; Thompson-Fawcett et al, 2001). Neoplastic change in the
reservoir has been principally demonstrated arising from remaining rectal mucosa (the cuff) at the lower
aspect of the reservoir. Colonic phenotypic change in ileal mucosa, in combination with inflammatory
change and associated epithelial hyperproliferation, at least suggests the potential for increased
neoplastic risk of the ileal mucosa in the reservoir (Shepherd, 1990). In the experience of most groups,
dysplasia and carcinoma, in the ileal reservoir mucosa of ulcerative colitis patients, are extremely
rare. However, workers from Sweden have intensively studied patients over many years with multiple
endoscopies and biopsies and they have demonstrated relatively high rates of dysplasia (in ulcerative
colitis patients): in their studies about 10% of reservoir patients develop the most florid inflammatory
changes with severe villous atrophy. It is this group that is subject to pouchitis and 71% of patients
in this group have had dysplasia including one with high grade dysplasia (Veress et al, 1995; Gullberg et
These studies would suggest that there is potential for neoplastic change within the ileal mucosa of
the pelvic ileal reservoir in UC patients. For management purposes, it would seem that the highest risk
is with those patients with the most advanced pathological changes, those most likely to develop
pouchitis. As this patient group can, seemingly, be identified within six months of ileostomy reversal
(Setti Carraro et al, 1994 & 1998), it would seem that these patients should be selected for the most
comprehensive surveillance. Management for reservoir mucosal dysplasia should be similar to that for
Currently we should maintain a balanced attitude toward neoplastic risk in the pouch. Dysplasia, in
native ileal mucosa, has only been described from one centre and no other centre has yet seen such levels
of dysplastic changes. On the other hand there is concern about the pouch in FAP and about the remaining
rectal 'cuff' in UC patients. There is now increasing evidence (Ziv et al, 1994; Remzi et al, 2003) of
cuff dysplasia but it remains uncertain what the likely progression to cancer is. It is clear that the
cuff, as well as those with type C pouch pathology, demand close surveillance (McLeod et al, 2006).
Newer endoscopic techniques, especially high-magnification chromoscopic pouchoscopy, may be of
considerable value for the surveillance of the pouch and the columnar cuff (Hurlstone et al, 2004).
4. Has histology aided our understanding of diversion disease?
Diversion colitis is an iatrogenic inflammation of the large bowel, induced by diversion of the
faecal stream. Colon is most often excluded from the faecal steam during Hartmann's operation for
obstruction of the sigmoid colon and/or rectum, most often for carcinoma or complicated diverticular
disease. Diversion is performed for varied paediatric conditions, especially Hirschsprung's disease.
Inflammatory bowel disease may also be an indication for diversion: in Crohn's disease to ameliorate the
disease whilst, in ulcerative colitis, the rectum is defunctioned during the three-stage ileal pouch
procedure. Diversion proctocolitis is associated with characteristic macroscopic and histological
features. Despite this, symptomatology is very variable. Although pathological changes do occur in the
majority of diverted large intestines, by no means all patients suffer symptoms. Rectal bleeding, mucus
diarrhoea and abdominal pain are all described but are not consistent features of the disease.
Despite much literature suggesting the opposite, the cause of diversion colitis remains uncertain.
Harig et al (1989) first suggested that butyrate, the preferred metabolic substrate for colonic
epithelial cells, was deficient in the diverted colon and rectum and that this deficiency was the cause
of diversion pathology. In support of their theorem they induced clinical remission of the disease by
the instillation of butyrate enemas. Against this evidence is the only controlled trial of butyrate,
which has shown no significant improvement, compared to controls (Guillemot et al, 1991). The same group
have observed reduction of strict anaerobes in the defunctioned intestine and have suggested that this
altered microflora may directly induce inflammation (Neut et al, 1989) whilst, more recently, they have
suggested that increased nitrate-reducing bacteria may be a factor in the induction of inflammation (Neut
et al, 1997). The exact aetiopathogenesis of inflammation in diversion proctocolitis remains uncertain
and further research is needed.
There has been much perplexity over the histological changes seen in diverted large intestine. This
is largely because it has only been recently appreciated that the histological features of the disease
vary according to the nature of the disease, if any, for which the bowel was diverted (Warren &
Shepherd, 1992 & 2000; Edwards et al, 1999). For instance the appearances of the rectum,
defunctioned after total colectomy in chronic ulcerative colitis, are very different from those of
diverted colon in Crohn's disease (Warren & Shepherd 1992). The most characteristic histological
feature of diversion is lymphoid follicular hyperplasia (Yeong et al, 1991). This is apparent
endoscopically as the nodularity that is so characteristic of the disease, especially in children. The
nodules may show overlying aphthoid ulceration and this should not be taken to represent Crohn's disease
(Lusk et al, 1984). The great majority of diverted intestines show mucosal abnormality but the severity
and pattern of the disease are very variable and not predictable by the length of time the bowel has been
diverted (Komorowski, 1990; Geraghty & Talbot, 1991). Thus there is a histological spectrum from
mild chronic inflammation and crypt architectural distortion through to florid active inflammation
mimicking active chronic inflammatory bowel disease, especially ulcerative colitis (Komorowski, 1990; Ma
et al, 1990; Warren & Shepherd, 2000). Such mimicry is further fuelled by the occasional observation
of well-defined epithelioid cell granulomata in the mucosa of diversion colitis (Ma et al, 1990; Warren
& Shepherd, 1992). This, alone, should not be taken as evidence of Crohn's disease. The
histological changes of diversion are apparent within three months of defunctioning and may be rapidly
restored to normality by re-anastomosis (Warren & Shepherd, 2000).
5. Should assessment of a diverted bowel segment provoke a change in the diagnosis of the type of inflammatory bowel disease?
The answer to this is usually 'No'. Diversion, just like pouch pathology, may provoke profound
mimicry of other inflammatory conditions, especially Crohn's disease, and it is essential that the
evidence for such a change of diagnosis is sought, not in intestine that has been subject to all sorts of
new provoking insults and environmental changes, but in 'virginal' pathology, most notably, in the case
of the colectomy performed for CIBD, in that colectomy specimen and in pre-existing biopsies. This is
particularly so for the proctectomy specimen, removed during the three-stage pouch procedure.
Defunctioning the rectum in patients with ulcerative colitis may induce florid inflammatory changes.
These may be manifest clinically and endoscopically as a severe active proctitis with nodularity and
ulceration, which may be more severe than the original ulcerative colitis affecting the rectum.
Histologically, the rectal stump shows the characteristic features of ulcerative colitis together with
florid lymphoid hyperplasia (the endoscopic nodularity) and, often, ulceration (frequently overlying
hyperplastic lymphoid follicles)(Warren et al, 1993). In addition, fissures, mucosal granulomas and
patchiness of inflammation are seen. It is easy to see how these changes may be misconstrued as Crohn's
disease by inexperienced observers, especially as transmural inflammation in the form of lymphoid
aggregates is also a characteristic feature (Warren et al, 1993). We believe that the confusing
histological changes seen in rectal stumps result from a combination of diversion proctitis and
pre-existing ulcerative colitis and that the pathological diagnosis of inflammatory bowel disease should
be restricted to the macroscopic and microscopic assessment of the colectomy specimen, together with the
clinical, radiological and endoscopic assessment of the whole patient (Warren et al, 1993). A diagnosis
of Crohn's disease should not be based solely on the histopathological appearances seen in the
defunctioned rectum (Warren & Shepherd, 2000).
One curiosity of diversion disease, and indeed of chronic inflammatory bowel disease, is the fact
that the pathology (and, usually, the clinical features) of ulcerative colitis frequently worsens in
diverting the faecal stream and yet the pathology of Crohn's disease improves when the colon is
defunctioned (Edwards et al, 1999). In addition to the changes that may induce mimicry of Crohn's
disease, namely transmural inflammation, granulomas and fissures (Warren et al, 1993), the defunctioned
rectum in ulcerative colitis shows florid lymphoid follicular hyperplasia, evidence of activity in the
form of disruptive crypt abscesses and surface ulceration. A characteristic additional feature is the
presence of summit-type lesions with pseudomembrane formation, closely mimicking pseudomembranous colitis
(PMC)(Warren et al, 1993). It may be that these features represent a combination of the original
inflammatory bowel disease, enhanced by diversion-type pathology, with superimposed mucosal ischaemia to
account for the mimicry of PMC.
The rectum is diverted, in ulcerative colitis, to facilitate subsequent pouch surgery, not
necessarily in the hope of improving the disease. In Crohn's disease, the colon is diverted with disease
amelioration very much in mind. About two-thirds of patients with Crohn's colitis will achieve sustained
clinical remission subsequent to diversion, which may also be effective for perianal Crohn's disease that
fails to respond to other measures, although occasionally perianal disease may rapidly worsen (Warren
& Shepherd, 2000). Reconnection of the faecal steam induces recurrent disease in approximately 40%
of those diverted for Crohn's colitis. Systematic pathological review of the diverted colon in Crohn's
disease has not been undertaken but some notable observations have been made. Firstly the colon shows
considerable reduction in luminal diameter, a feature that may also been seen in diversion of the colon
and rectum, performed upon normal bowel or that affected by ulcerative colitis. This involution may
provide difficulties for the surgeon attempting re-anastomosis. Histologically there is reduction in
ulceration and both acute and chronic inflammation. Granulomas are usually regarded as transient
features in Crohn's disease and this has been used to explain why Crohn's granulomas do not often contain
such calcified bodies (unlike in sarcoidosis in which the granulomas are thought to represent a
long-standing characteristic). A distinctive feature of diverted Crohn's colitis is the presence of
granulomas containing calcified Schaumann bodies (Warren & Shepherd, 2000).
Should Crohn's colitis relapse after re-anastomosis subsequent to a period of diversion, often the
only course of action is total proctocolectomy. The interpretation of the histopathology of such a
resected specimen also requires caution. Partial resolution of the Crohn's colitis with the superimposed
histological changes of diversion colitis may produce pathology indistinguishable from ulcerative
colitis. The danger here is that the preceding clinicopathological and radiological evidence for Crohn's
colitis may be overlooked. Fortunately in most cases adequate provision of blocks for histological
examination will reveal transmural inflammation in the form of lymphoid aggregates or evidence of
granulomatosis, particularly deep within the wall. The isolated histopathological reporting of the
resected colon following diversion and reconnection can result in an erroneous diagnosis, as surely as
the isolated reporting of the defunctioned rectum in ulcerative colitis. This author strongly recommends
that all resections and biopsies are reviewed before a change of diagnosis is contemplated in patients
with inflammatory bowel disease who have undergone these forms of surgery.
- de Silva HJ, Millard PR, Kettlewell M, Mortensen N, Prince C, Jewell DP. Mucosal characteristics of
pelvic ileal pouches. Gut 1991; 32: 61-65.
- Edwards CM, George BD, Warren BF. Diversion colitis: new light through old windows. Histopathology
1999; 35: 86-7.
- Fruin AB, El-Zammer O, Stucchi AF, O'Brien M, Becker JM. Colonic metaplasia in the ileal pouch is
associated with inflammation and is not the result of long-term adaptation. J Gastro Surg 2003; 7:
- Geraghty JM, Talbot IC. Diversion colitis: histological features in the colon and rectum after
defunctioning colostomy. Gut 1991; 32: 1020-3.
NS , Sanford WW, Bodzin JH. Crohn's-like complications in patients with ulcerative colitis after total
proctocolectomy and ileal pouch-anal anastomosis. Am J Surg Pathol 1997; 21: 1343-1353.
- Guillemot F, Colombel JF, Neut C, Verplanck N, Lecomte M, Romond C, Paris JC, Cortot A. Treatment of
diversion colitis by short-chain fatty acids. Prospective and double-blind study. Dis Colon Rectum
1991; 34: 861-4.
- Gullberg K, Stahlberg D, Liljeqvist L, Tribukait B, Reinholt FP, Veress B, Lofberg R. Neoplastic
transformation of the pelvic pouch mucosa in patients with ulcerative colitis. Gastroenterology 1997;
- Gustavsson S, Weiland LH, Kelly KA. Relationship of backwash ileitis to ileal pouchitis after
ileoanal anastomosis. Dis Colon Rectum 1987; 30: 25-28.
- Harig JM, Soergel KH, Komorowski RA, Wood CM. Treatment of diversion colitis with short-chain-fatty
acid irrigation. New Engl J Med 1989; 320: 23-8.
- Hata K, Watanabe T, Shinozaki M, Nagawa H. Patients with extra-intestinal manifestations have a
higher risk of developing pouchitis in ulcerative colitis: multivariate analysis. Scand J Gastroenterol
2003; 38: 1055-1058.
- Hurlstone DP, Shorthouse AJ, Cross SS, Brown S, Sanders DS, Lobo AJ. High-magnification chromoscopic
pouchoscopy: a novel in vivo technique for surveillance of the anal transition zone and columnar cuff
following ileal pouch-anal anastomosis. Techniques in Coloproctology 2004; 8: 173-8.
- Komorowski RA. Histologic spectrum of diversion colitis. Am J Surg Pathol 1990; 14: 548-54.
- Lohmuller JL, Pemberton JH, Dozois RR, Ilstrup D. The relationship between pouchitis after pouch-anal
anastomosis and extra-intestinal manifestations of chronic ulcerative colitis. Ann Surg 1990; 211:
- Lucarotti ME, Freeman BJ, Warren BF, Durdey P. Synchronous proctocolectomy and ileoanal pouch
formation and the risk of Crohn's disease. Br J Surg 1995; 82: 755-6.
- Lusk LB, Reichen J, Levine JS. Aphthous ulceration in diversion colitis. Clinical implications.
Gastroenterology 1984; 87: 1171-3.
- Luukkonen P, Jarvinen H, Tanskanen M, Kahri A. Pouchitis - recurrence of the inflammatory bowel
disease? Gut 1994; 35: 243-6.
- Ma CK, Gottlieb C, Haas PA. Diversion colitis: a clinico-pathological study of 21 cases. Hum Pathol
1990; 21; 4: 29 -36.
- MacNeill KN, Guindi M, Riddell RH. Is transmural inflammation in the ileoanal pouch significant? Mod
Pathol 2004; 17: 123A.
- McLeod RS & the Surgical Task Force, International Organization for the Study of Inflammatory
Bowel Diseases (IOIBD). Risk of dysplasia and cancer in patients with an ileal pouch-anal anastomosis
for ulcerative colitis: review of the literature and guidelines for long-term follow-up. 2006: in
MN , Mortensen N, Kettlewell M, Jewell DP. Smoking may prevent pouchitis in patients with restorative
proctocolectomy for ulcerative colitis. Gut 1996; 38: 362-4.
- Mimura T, Rizzello F, Helwig U, Poggioli G, Schreiber S, Talbot IC, Nicholls RJ, Gionchetti P,
Campieri M, Kamm MA. Once daily high dose probiotic therapy (VSL#3) for maintaining remission in
recurrent or refractory pouchitis. Gut 2004; 53: 108-14.
- Mortensen NJMcC, Madden MV. Pouchitis - acute inflammation in ileal pouches. In: Nicholls RJ,
Bartolo DCC, Mortensen NJMcC (eds). Restorative proctocolectomy. Oxford:
Blackwell Scientific Publications 1993; 119-131.
- Neut C, Colombel JF, Guillemot F, Cortot A, Gower P, Quandalle P, Ribet M, Romond C, Paris JC.
Impaired bacterial flora in human excluded colon. Gut 1989; 30: 1094-8.
- Neut C, Guillemot F, Colombel JF. Nitrate-reducing bacteria in diversion colitis: a clue to
inflammation?. Dig Dis Sci 1997; 42: 2577-80.
- Nugent KP, Spigelman AD, Nicholls RJ, Talbot IC, Neale K, Phillips RKS. Pouch adenomas in patients
with familial adenomatous polyposis. Br J Surg 1993; 80: 1620.
- Penna C, Dozois RR, Tremaine W, Sandborn W, LaRusso N, Schleck C, Ilstrup D. Pouchitis after ileal
pouch-anal anastomosis for ulcerative colitis occurs with increased frequency in patients with associated
primary sclerosing cholangitis. Gut 1996; 38: 234-239.
- Remzi FH, Fazio VW, Delaney CP, Preen M, Ormsby A, Bast J, O'Riordain MG, Strong SA, Church JM, Petras
RE, Gramlich T, Lavery IC. Dysplasia of the anal transitional zone after ileal pouch-anal anastomosis:
results of prospective evaluation after a minimum of ten years. Dis Col Rect 2003; 46: 6-13.
- Samarasekera DN, Stebbing JF, Kettlewell MG, Jewell DP, Mortensen NJ. Outcome of restorative
proctocolectomy with ileal reservoir for ulcerative colitis: comparison of distal colitis with more
proximal disease. Gut 1996; 38: 574-7.
- Sanborn WJ, Pardi DS. Clinical management of pouchitis. Gastroenterology 2004; 127: 1809-14.
- Setti Carraro P, Talbot IC, Nicholls RJ. Longterm appraisal of the histological appearances of the
ileal reservoir after restorative proctocolectomy for ulcerative colitis. Gut 1994; 35: 1721-1727.
- Setti Carraro P, Talbot IC, Nicholls RJ. Patterns of distribution of endoscopic and histological
changes in the ileal reservoir after restorative proctocolectomy for ulcerative colitis. A long-term
follow-up study. Int J Colorectal Dis 1998; 13: 103-7.
- Shepherd NA. The pelvic ileal reservoir: pathology and pouchitis. Neth J Med 1990; 37: S57-S64.
- Shepherd NA. Pouchitis and neoplasia in the pelvic ileal reservoir. Gastroenterology 1995; 109:
- Shepherd NA, Healey CJ, Warren BF, Richman PI, Thomson WHF, Wilkinson SP. Distribution of mucosal
pathology and an assessment of colonic phenotypic change in the pelvic ileal reservoir. Gut 1993; 34:
- Shepherd NA, Jass JR, Duval I, Moskowitz RL, Nicholls RJ, Morson BC. Restorative proctocolectomy with
ileal reservoir: pathological and histochemical study of mucosal biopsy specimens. J Clin Pathol 1987;
- Thompson-Fawcett MW, Marcus VA, Redston M, Cohen Z, McLeod RS. Adenomatous polyps develop commonly
in the ileal pouch of patients with familial adenomatous polyposis. Dis
Col Rect 2001; 44: 347-53.
- Veress B, Reinholt FP, Lindquist K, Lofberg R, Liljeqvist L. Long-term histomorphological surveillance
of the pelvic ileal pouch: dysplasia develops in a subgroup of patients. Gastroenterology 1995; 109:
- Warren BF, Shepherd NA. Diversion proctocolitis. Histopathology 1992; 21: 91-94.
- Warren BF, Shepherd NA. Pouch pathology. In Restorative proctocolectomy (eds Nicholls RJ, Bartolo
DCC, Mortensen NJMcC). Blackwell Scientific Publications Ltd, Oxford : 1993; 147-162.
- Warren BF, Shepherd NA, Bartolo DC, Bradfield JW. Pathology of the defunctioned rectum in ulcerative
colitis. Gut 1993; 34: 514-6.
- Warren BF, Shepherd NA. Surgical pathology of the intestines: the pelvic ileal reservoir and
diversion enterocolitis. In Recent Advances in Histopathology, (eds Lowe DG, Underwood JCE), volume 18,
Churchill Livingstone, Edinburgh: 2000, 63-88.
- Yantiss RK, Odze RD. Diagnostic difficulties in inflammatory bowel disease pathology.
Histopathology 2006; 48: 116-132.
- Yeong ML, Bethwaite PB, Prasad J, Isbister WH. Lymphoid follicular hyperplasia - a distinctive
feature of diversion colitis. Histopathology 1991; 19: 55 -61.
- Ziv Y, Fazio VW, Sirimarco MT, Lavery IC, Goldblum JR, Petras RE. Incidence, risk factors and
treatment of dysplasia in the anal transitional zone after ileal pouch-anal anastomosis. Dis Colon
Rectum 1994; 37: 1281-1285.